It is well known in the art that the storage life of certain injectable substances, such as glucagon, is increased when the substance is stored in a powdered state. Lyophilization is one way of producing a powdered substance from a liquid based material. It involves a rapid freezing of the material at a very low temperature followed by a rapid dehydration by sublimation in a high vacuum. The resulting lyophilized substance is typically stored in a glass vial or cartridge which is closed by a cap, such as a rubber stopper or septum.
It is necessary to reconstitute the powdered or solid substance prior to administration. This is accomplished by mixing the powdered substance with a suitable diluent or liquid. Reconstitution is traditionally performed using a syringe with a needle to withdraw the diluent from one separate vial and inject it into another separate vial containing the powdered compound, whereupon the latter vial is shaken or swirled to thoroughly mix the two constituents. The syringe with needle is then used to withdraw from this vial the desired amount of reconstituted drug to be injected into the patient. Because two separate containers are used, the person reconstituting the compound must be certain to mix the correct amounts such that a proper concentration of the mixture results. When a syringe is used to mix the diluent and the drug, an exact diluent to drug ratio is difficult to obtain. This brings about some uncertainty regarding the exact concentration of administered drug.
Moreover, because the diluent and the compound are in separate, sterilized containers, and the diluent is manually withdrawn from the diluent container via a syringe with a needle, and the syringe is subsequently moved from the diluent container to the compound container for injection of the diluent into the compound container, both sterility and safety are in risk of being compromised.
Because of an increased use of powdered compounds or lyophilized drugs it is desirable to provide both professionals and non-professionals with a simple and reliable system that facilitates preparation of an accurate dosage of a mixed product, e.g. a reconstituted compound.
In addition, it is desirable to provide a system that can reconstitute a lyophilized drug without potential hazards to the user while maintaining sterility throughout the process.
U.S. Pat. No. 5,466,220 discloses a mixing device comprising a base on which a syringe and two vials are mounted together with a T-shaped connector piece. Retainers hold the two vials in place at a predetermined spacing from their respective connectors prior to operation of the device. The device is kept within a protective sterile packaging until the vials are pushed into their respective connectors allegedly providing a system that is sealed during the entire reconstitution process.
U.S. Pat. No. 6,364,865 discloses different embodiments of medication delivery systems and transfer systems for forming a solution from constituents from a set of vials respectively containing a lyophilized compound and a diluent.
Sometimes a desired dose of a drug solution exceeds the amount corresponding to the drug contained in a single set of vials. In this case the total dose must be composed using lyophilized drug from two or more vial sets, the number of vial sets corresponding to the desired dose. This may, e.g., be done by sequentially applying a solvent liquid to each of the vials and retrieving the reconstituted drug to one common reservoir or syringe. When the drug of all of the vials has been reconstituted in this manner, the total dose may be administered to the person from the common reservoir or syringe. Reconstituting lyophilized drug from two or more vials in this manner is, however, relatively time consuming. Furthermore, there is a risk of contamination of the drug due to the number of times a free opening will be exposed to free air or dirt.
It is therefore desirable to provide a mixing system which facilitates mixing a dose using powdered drug from two or more vials, also known as pooling, and which reduces the risk of contamination of the resulting drug.
WO 2007/122209 discloses a transfer system comprising a container unit holding two containers and a transfer unit adapted to be coupled to the container unit for enabling a mixing of the contents of the two containers, wherein a pressure generator, such as a syringe, is used to force the contents of the one container to move to the other container via a channel in the transfer unit fluidly connecting the two containers.
When emptying the container containing the final mixed product the influence of included air should be minimised in order to avoid foaming of the drug. Two factors which may contribute to the generation of foam in a system as described in WO 2007/122209 are the flow rate of the drug solution when transferred from the container to the syringe and air that is potentially aspired from other parts of the system such as the solvent container.
It is desirable to provide a mixing system which substantially eliminates the issue of foaming. Avoiding foaming is highly important for several kinds of drugs, in particular drugs that must be given intravenously, such as recombinant factor products for the treatment of haemophilia patients.